Research in The Unit on Cognitive Neurophysiology and Imaging (UCNI) benefits enormously from its use of fMRI in monkeys, which provides us with a parallax onto the brain: as described in a different project, the fMRI and neurophysiological signals frequently disagree. Rather than seeing this disagreement as a liability, we are eager to understand it and exploit the different windows on brain function that the two methods provide. In this spirit, much of our work is in close correspondence with the neighboring Neurophysiology Imaging Facility (NIF), where trained monkeys are scanned routinely while viewing a variety of visual stimuli. The repertoire of the NIF includes simultaneous neurophysiological recordings, microinfusion, and electrical microstimulation in the magnet, and offers a range of unique tools to study brain physiology related to sensation and perception. We have taken four main approaches to studying how fMRI responses relate to neural processes in the brain. [unreadable] [unreadable] The first approach, described in detail in a different project description, is to use stimuli for which the neural and fMRI signal become dissociated during perceptual suppression. This approach has measured the fMRI signal and single-neuron response in the primary visual cortex (V1) of monkeys during perceptual suppression. The monkeys were trained to report whether they perceived a salient target. We found that on trials in which the target was invisible, the fMRI responses showed a major drop, while spiking responses of neurons in the same area did not change their activity. Indeed, careful analysis revealed that the fMRI and neural signals are inherently different under condition in which perception does not match the physical stimulus condition.[unreadable] [unreadable] The second approach has been to inactivate portions of the brain locally using a GABA agonist (muscimol), and then examine the changes in functional activity in other brain regions. This has been an effective tool, permitting the unprecedented visualization of global patterns of activity following local inactivation. This project is designed to examine corticothalamic interplay and its contribution to cortical responses.[unreadable] [unreadable] The third approach involves recording in the brain during fMRI scanning using implanted multicontact electrodes. During scanning sessions, activity in different layers of the primary visual cortex are monitored. This permits us to monitor covariation in the activity fluctuations of in neural and fMRI signals. Our initial findings, published this year, and to be presented at the upcoming Society for Neuroscience meeting, is that neural activity in V1 his highly correlated with fMRI activity fluctuations throughout the cerebral cortex, even far away from the visual cortex itself. We are studying this topic intensely, as the reason for this widespread correlation will have implications for understanding the variability in cortical responses more generally.[unreadable] [unreadable] Finally, the fourth approach is the use of electrical microstimulation inside the magnetic bore during functional imaging. This technique has recently been used to infer structural and functional connectivity between areas, with functional activation far away from the site of stimulation indicating such a connection. Our preliminary results stimulating the superior colliculus have shown activation in the striate and extrastriate visual cortex. The extent to which these response reflect the firing of neurons in these areas is a matter of question, that we plan to address in the coming year.[unreadable] [unreadable] These approaches, taken together, have allowed us to perform experiments that can only be achieved in this unique NIH environment. Our close collaboration with the Neurophysiology Imaging Facility recently led to a publication in which we examined the connection between fMRI and neural signals. Ongoing experiments will continue to exploit the capacity to combine invasive electrophysiological and pharmacological experiments with fMRI, to gain a mechanistic perspective on the neural and imaging signals that predominate the neuroscience literature.